Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort.

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis type 2 (NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event (CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32 female), median age 24.5 years (range 11-66 years), were followed for a median of 32.7 months (range 12.0-60.2 months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24 %) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5 %) had proteinuria. Of 36 patients followed for 36 months, 78 % were free from hypertension and 86 % were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be independent predictors of development of hypertension with dose of 7.5 mg/kg 3 weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.

Glioblastoma and radiotherapy: A multicenter AI study for Survival Predictions from MRI (GRASP study).

BACKGROUND: The aim was to predict survival of glioblastoma at 8 months after radiotherapy (a period allowing for completing a typical course of adjuvant temozolomide), by applying deep learning to the first brain MRI after radiotherapy completion. METHODS: Retrospective and prospective data were collected from 206 consecutive glioblastoma, isocitrate dehydrogenase -wildtype patients diagnosed between March 2014 and February 2022 across 11 UK centers. Models were trained on 158 retrospective patients from 3 centers. Holdout test sets were retrospective (n = 19; internal validation), and prospective (n = 29; external validation from 8 distinct centers). Neural network branches for T2-weighted and contrast-enhanced T1-weighted inputs were concatenated to predict survival. A nonimaging branch (demographics/MGMT/treatment data) was also combined with the imaging model. We investigated the influence of individual MR sequences; nonimaging features; and weighted dense blocks pretrained for abnormality detection. RESULTS: The imaging model outperformed the nonimaging model in all test sets (area under the receiver-operating characteristic curve, AUC P = .038) and performed similarly to a combined imaging/nonimaging model (P > .05). Imaging, nonimaging, and combined models applied to amalgamated test sets gave AUCs of 0.93, 0.79, and 0.91. Initializing the imaging model with pretrained weights from 10 000s of brain MRIs improved performance considerably (amalgamated test sets without pretraining 0.64; P = .003). CONCLUSIONS: A deep learning model using MRI images after radiotherapy reliably and accurately determined survival of glioblastoma. The model serves as a prognostic biomarker identifying patients who will not survive beyond a typical course of adjuvant temozolomide, thereby stratifying patients into those who might require early second-line or clinical trial treatment.

Factors associated with survival in small cell lung cancer: an analysis of real-world national audit, chemotherapy and radiotherapy data.

BACKGROUND: The mainstay of treatment for small cell lung cancer (SCLC) involves platinum doublet chemotherapy but the optimal duration, 4 vs. 6 cycles, is not known. Concurrent thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is recommended for fit individuals with limited stage. However, outside of clinical trials, the efficacy of sequential thoracic radiotherapy and PCI for extensive stage is uncertain. METHODS: This retrospective, observational, cohort study used English national lung cancer data to determine the factors associated with survival for all people diagnosed with SCLC. More precisely, for individuals who received chemotherapy, we examined survival by the chemotherapy duration, thoracic radiotherapy dose and the use of PCI. RESULTS: In total 6,438 people were diagnosed with SCLC. We identified that male sex (OR 0.7; 95% CI: 0.62-0.80), increasing age (P=0.01) greater comorbidity (P≤0.01), extensive stage (OR 0.21; 95% CI: 0.19-0.25) and worse performance status (PS2 vs. PS0 adjusted OR 0.38 95% CI: 0.31-0.48) were associated with reduced 1-year survival. Receipt of chemotherapy augmented survival. We analysed data for 1,761 people who had received chemotherapy. Thoracic radiotherapy (≥30 Gy for extensive stage and ≥40 Gy for limited stage) and PCI were independently associated with better survival (P≤0.01 for each), but 6 cycles of chemotherapy instead of 4 was not (limited stage adjusted OR 0.97; 95% CI: 0.48-1.97) extensive stage adjusted OR 1.34; 95% CI: 0.81-2.21). CONCLUSIONS: Extending chemotherapy beyond 4 cycles to 6 does not augment survival. Appropriately prescribed thoracic radiotherapy and PCI can prolong survival in both limited and extensive stage SCLC.

Hypoxia imaging with [18F]HX4 PET in squamous cell head and neck cancers: a pilot study for integration into treatment planning.

BACKGROUND: Radical chemoradiotherapy is the primary treatment for head and neck cancers in many hospitals. Tumour hypoxia causes radiotherapy resistance and is an indicator of poor prognosis for patients. Identifying hypoxia to select patients for intensified or hypoxia-modified treatment regimens is therefore of high clinical importance. PATIENTS AND METHODS: We evaluated hypoxia in a group of patients with newly diagnosed squamous cell head and neck cancer using the hypoxia-selective radiotracer [F]HX4. Patients underwent a single [F]HX4 PET/computed tomography scan prior to beginning chemoradiotherapy. RESULTS: Three out of eight patients recruited were scanned with [F]HX4. Two out of three had pretreatment [F]FDG PET/computed tomography scans available for review. [F]HX4 tumour uptake varied between patients, with tumour to mediastinal ratios ranging from 1 to 3.5. CONCLUSION: The spectrum of [F]HX4 uptake in this small series of patients exemplifies the difference in oxygenation profiles between histologically similar tumours. Performing an additional PET scan with [F]HX4 prior to chemoradiotherapy treatment was logistically challenging in a routine setting, and therefore validation of its clinical impact should be the focus of future studies [EudraCT number 2013-003563-58].